UBP25_MOUSE
ID UBP25_MOUSE Reviewed; 1055 AA.
AC P57080; Q80ZT9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 25;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 25;
DE AltName: Full=Ubiquitin thioesterase 25;
DE AltName: Full=Ubiquitin-specific-processing protease 25;
DE Short=mUSP25;
GN Name=Usp25;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=10644437; DOI=10.1006/geno.1999.6025;
RA Valero R., Marfany G., Gonzalez-Angulo O., Gonzalez-Gonzalez G.,
RA Puelles L., Gonzalez-Duarte R.;
RT "USP25, a novel gene encoding a deubiquitinating enzyme, is located in the
RT gene-poor region 21q11.2.";
RL Genomics 62:395-405(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP STRUCTURE BY NMR OF 1-67.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-013, a UBA domain in mouse.";
RL Submitted (SEP-2004) to the PDB data bank.
RN [5]
RP ALTERNATIVE SPLICING, DEVELOPMENTAL STAGE, POSSIBLE FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16501887; DOI=10.1007/s00018-005-5533-1;
RA Bosch-Comas A., Lindsten K., Gonzalez-Duarte R., Masucci M.G., Marfany G.;
RT "The ubiquitin-specific protease USP25 interacts with three sarcomeric
RT proteins.";
RL Cell. Mol. Life Sci. 63:723-734(2006).
RN [6]
RP INDUCTION.
RX PubMed=27129230; DOI=10.1074/jbc.m116.718080;
RA Ren Y., Zhao Y., Lin D., Xu X., Zhu Q., Yao J., Shu H.B., Zhong B.;
RT "The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of
RT Usp25 Gene.";
RL J. Biol. Chem. 291:13206-13215(2016).
CC -!- FUNCTION: Deubiquitinating enzyme that hydrolyzes ubiquitin moieties
CC conjugated to substrates and thus, functions to process newly
CC synthesized Ubiquitin, to recycle ubiquitin molecules or to edit
CC polyubiquitin chains and prevents proteasomal degradation of
CC substrates. Hydrolyzes both 'Lys-48'- and 'Lys-63'-linked
CC tetraubiquitin chains (By similarity). {ECO:0000250}.
CC -!- FUNCTION: The muscle-specific isoform (USP25m) may have a role in the
CC regulation of muscular differentiation and function.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12;
CC -!- SUBUNIT: Homodimer or oligomer (By similarity). Interacts with ACTA1
CC (via its C-terminus); the interaction occurs for all isoforms but is
CC strongest for isoform USP25m in muscle differentiating cells. Interacts
CC (isoform USP25m only) with MYBPC1; the interaction prevents proteasomal
CC degradation of MYBPC1. Interacts (isoform USP25m only) with FLNC (via
CC filament repeats 17-18, 20-21 and 24). Interacts with GAPDH. Interacts
CC with SUMO3; the interaction sumoylates efficiently USP25. Interacts
CC with SUMO2; the interaction sumoylates efficiently USP25. Interacts
CC with SUMO1; the interaction only weakly sumoylates USP25. Interacts
CC with SYK; phosphorylates USP25 and regulates USP25 intracellular levels
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16501887}. Nucleus
CC {ECO:0000269|PubMed:16501887}. Note=The longer muscle-specific isoform
CC (USP25m) Some transient punctuate nuclear location in myotubes during
CC myocyte development.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=A longer muscle-specific isoform, USP25m, also exists.;
CC Name=1;
CC IsoId=P57080-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Highly expressed in testis especially in primary
CC and secondary spematocytes and in immature spermatids. Also found in
CC brain, skeletal muscle, liver and heart. {ECO:0000269|PubMed:10644437}.
CC -!- DEVELOPMENTAL STAGE: At 13.5 dpc and 16.5 dpc, expression in the brain
CC correlates with the proliferate ventricular zone and post-mitotic
CC neurons of the intermediate zone, particularly in the forebrain. More
CC marked expression at 16.5 dpc in the telencephalic septum and in the
CC pallium. In myocytes, expressed throughout differentiation of myotubes.
CC {ECO:0000269|PubMed:10644437, ECO:0000269|PubMed:16501887}.
CC -!- INDUCTION: Induced by type I interferons (IFNA and IFNB1) produced in
CC response to lipopolysaccharide (LPS) and viral infection (HIV-1 and SeV
CC viruses) (at protein level). {ECO:0000269|PubMed:27129230}.
CC -!- PTM: Acetylated. {ECO:0000250}.
CC -!- PTM: Sumoylation impairs binding to and hydrolysis of ubiquitin chains.
CC Sumoylated preferentially with SUMO2 or SUMO3. Desumoylated by SENP1.
CC Regulated by ubiquitination on the same residue (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Preferentially monoubiquitinated but can also be
CC polyubiquitinated. Autodeubiquitinated. Ubiquitination activates the
CC enzymatic activity either by preventing sumoylation or by allowing
CC novel interactions (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation in the C-terminal by SYK regulates USP25 cellular
CC levels. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF170563; AAF32264.1; -; mRNA.
DR EMBL; BC048171; AAH48171.1; -; mRNA.
DR EMBL; BC063059; AAH63059.1; -; mRNA.
DR CCDS; CCDS28275.1; -. [P57080-1]
DR RefSeq; NP_038946.2; NM_013918.2. [P57080-1]
DR PDB; 1VDL; NMR; -; A=1-67.
DR PDBsum; 1VDL; -.
DR AlphaFoldDB; P57080; -.
DR BMRB; P57080; -.
DR SMR; P57080; -.
DR BioGRID; 206017; 4.
DR IntAct; P57080; 2.
DR STRING; 10090.ENSMUSP00000023580; -.
DR MEROPS; C19.041; -.
DR iPTMnet; P57080; -.
DR PhosphoSitePlus; P57080; -.
DR EPD; P57080; -.
DR MaxQB; P57080; -.
DR PaxDb; P57080; -.
DR PeptideAtlas; P57080; -.
DR PRIDE; P57080; -.
DR ProteomicsDB; 297794; -. [P57080-1]
DR Antibodypedia; 5805; 263 antibodies from 30 providers.
DR DNASU; 30940; -.
DR Ensembl; ENSMUST00000023580; ENSMUSP00000023580; ENSMUSG00000022867. [P57080-1]
DR GeneID; 30940; -.
DR KEGG; mmu:30940; -.
DR UCSC; uc007zsb.1; mouse. [P57080-1]
DR CTD; 29761; -.
DR MGI; MGI:1353655; Usp25.
DR VEuPathDB; HostDB:ENSMUSG00000022867; -.
DR eggNOG; KOG1863; Eukaryota.
DR GeneTree; ENSGT00940000157962; -.
DR HOGENOM; CLU_012188_0_0_1; -.
DR InParanoid; P57080; -.
DR OrthoDB; 194025at2759; -.
DR PhylomeDB; P57080; -.
DR TreeFam; TF329035; -.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR BioGRID-ORCS; 30940; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Usp25; mouse.
DR EvolutionaryTrace; P57080; -.
DR PRO; PR:P57080; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P57080; protein.
DR Bgee; ENSMUSG00000022867; Expressed in hindlimb stylopod muscle and 258 other tissues.
DR ExpressionAtlas; P57080; baseline and differential.
DR Genevisible; P57080; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000502; C:proteasome complex; ISS:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:MGI.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0032183; F:SUMO binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0007252; P:I-kappaB phosphorylation; IMP:MGI.
DR GO; GO:0006955; P:immune response; IMP:MGI.
DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; IDA:MGI.
DR GO; GO:0016071; P:mRNA metabolic process; IMP:MGI.
DR GO; GO:1904293; P:negative regulation of ERAD pathway; ISO:MGI.
DR GO; GO:0016579; P:protein deubiquitination; ISO:MGI.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISO:MGI.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IMP:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:MGI.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR003903; UIM_dom.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02809; UIM; 2.
DR SMART; SM00726; UIM; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50330; UIM; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Hydrolase;
KW Isopeptide bond; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Thiol protease; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..1055
FT /note="Ubiquitin carboxyl-terminal hydrolase 25"
FT /id="PRO_0000080654"
FT DOMAIN 14..57
FT /note="UBA-like"
FT DOMAIN 97..116
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 123..140
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 169..658
FT /note="USP"
FT REGION 77..102
FT /note="SUMO interaction domain (SIM)"
FT REGION 464..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 728..747
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 89..95
FT /note="Required for SUMO paralog-specific binding"
FT COMPBIAS 470..506
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 178
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT ACT_SITE 608
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UHP3"
FT MOD_RES 740
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UHP3"
FT CROSSLNK 99
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 99
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9UHP3"
FT CONFLICT 394
FT /note="E -> K (in Ref. 1; AAF32264)"
FT /evidence="ECO:0000305"
FT CONFLICT 496
FT /note="P -> L (in Ref. 1; AAF32264)"
FT /evidence="ECO:0000305"
FT CONFLICT 683
FT /note="P -> L (in Ref. 1; AAF32264)"
FT /evidence="ECO:0000305"
FT CONFLICT 841
FT /note="H -> L (in Ref. 1; AAF32264)"
FT /evidence="ECO:0000305"
FT HELIX 9..12
FT /evidence="ECO:0007829|PDB:1VDL"
FT HELIX 17..27
FT /evidence="ECO:0007829|PDB:1VDL"
FT HELIX 33..43
FT /evidence="ECO:0007829|PDB:1VDL"
FT HELIX 47..55
FT /evidence="ECO:0007829|PDB:1VDL"
SQ SEQUENCE 1055 AA; 121420 MW; 103E34EC3FA8A72B CRC64;
MTVEQNVLQQ SAAQKHQQTF LNQLREITGI NDAQILQQAL KDSNGNLELA VAFLTAKNAK
TPPQEETGYY QTALPGNDRY ISVGSQADAN VIDLTGDDKD DLQRAIALSL AESNRAFRET
GITDEEQAIS RVLEASIAEN KACLKRTPIE VWRDSRNPYD RKRQEKAPVG LKNVGNTCWF
SAVIQSLFNL LEFRRLVLNY KPPSNAQDLP RNQKEHRNLP FMRELRYLFA LLVGTKRKYV
DPSRAVEILK DAFKSNDSQQ QDVSEFTHKL LDWLEDAFQM KAEEETDEEK PKNPMVELFY
GRFLAMGVLE GKKFENTEMF GQYPLQVNGF KDLHECLEAA MIEGEIESLH SDNSGKSGQE
HWFTELPPVL TFELSRFEFN QALGRPEKIH NKLEFPQVLY LDRYMHRNRE ITRIKREEIK
RLKDYLTVLQ QRLERYLSYG SGPKRFPLVD VLQYALEFAS SKPVCTSPVD DIDASSSASG
PLPSQSLPST TEQQGPCASD LPGSSSPASG AALPLRSVIH KPFTQSRIPP DLPMHPAPRH
ITEEELCVLE SCLHRWRTEI ENDTRDLQES ISRIHRTIEL MYSDKSMIQV PYRLHAVLVH
EGQANAGHYW AYIFDHRESR WMKYNDIAVT KSSWEELVRD SFGGYRNASA YCLMYIDDKA
QFLIQEEFNK ETGQALVGME TLPPDLRDFV EEDNQRFEKE LEEWDTQLAQ RSLQEKLLAA
PKLREAEASA TTAQAGGADY LEQPSRSDLS KHWKEETLRV IAKASHDLED KGPETVLQSA
IKLEYSRLVK LAQEDTPPET DYRLHHVLVY FIQNQAPKKI IEKTLLEQFG DRNLSFDERC
HNIMKVAQAK LEMIKPEEVN LEEYEEWHAD YKKFRETTMY LITGLENFQR ESYIDSLLFL
LCAYQNNKEL LSKGPYRGHD GELISHYRRE CLLKLNEQAA ELFESGEDGD VNNGLIIMNE
FIVPFLPLLL VDDMEEKDIL AVEDMRNRWC SYLGQEMEAN LQEKLTDFLP KLLDCSTEIK
GFHEPPKLPS YSAHELCERF ARIMLSLSRT PADGR
